Fever regulation method and apparatus

ABSTRACT

A device and method for providing body cooling for treating fever. The cooling device applies cooling to blood flowing in a vein or artery, e.g., the vena cavae, that is then distributed throughout the body.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.10/411,001, filed Apr. 9, 2003, entitled “Fever Regulation Method AndApparatus,” which is a continuation of U.S. patent application Ser. No.10/005,416, filed Nov. 7, 2001, now U.S. Pat. No. 6,585,752, which is acontinuation-in-part of U.S. Patent Application Ser. Nos. 60/246,620,filed Nov. 7, 2000, entitled “Fever Regulation Method and Apparatus”;Ser. No. 09/586,000, filed Jun. 2, 2000, entitled “Method ForDetermining The Effective Thermal Mass Of A Body Or Organ Using ACooling Catheter,” now U.S. Pat. No. 6,383,210; Ser. No. 09/566,531,filed May 8, 2000, entitled “Method of Making Selective Organ CoolingCatheter,” now abandoned, which is a continuation of U.S. patentapplication Ser. No. 09/103,342, filed Jun. 23, 1998, entitled“Selective Organ Cooling Catheter And Method Of Using The Same,” nowU.S. Pat. No. 6,096,068, which is a continuation-in-part of U.S. patentapplication Ser. No. 09/047,012, filed Mar. 24, 1998, entitled“Selective Organ Hypothermia Method And Apparatus,” now U.S. Pat. No.5,957,963, which is a continuation-in-part of U.S. patent applicationSer. No. 09/012,287, filed Jan. 23, 1998, entitled “Selective OrganHypothermia Method And Apparatus,” now U.S. Pat. No. 6,051,019, all ofwhich are incorporated in their entireties by reference herein.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT

Not Applicable

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates generally to the lowering and control ofthe temperature of the human body. More particularly, the inventionrelates to a method and intravascular apparatus for cooling the wholebody, especially during periods of fever.

2. Background Information

Organs in the human body, such as the brain, kidney and heart, aremaintained at a constant temperature of approximately 37° C. Hypothermiacan be clinically defined as a core body temperature of 35° C. or less.Hypothermia is sometimes characterized further according to itsseverity. A body core temperature in the range of 33° C. to 35° C. isdescribed as mild hypothermia. A body temperature of 28° C. to 32° C. isdescribed as moderate hypothermia. A body core temperature in the rangeof 24° C. to 28° C. is described as severe hypothermia.

Hypothermia is uniquely effective in reducing brain injury caused by avariety of neurological insults and may eventually play an importantrole in emergency brain resuscitation. Experimental evidence hasdemonstrated that cerebral cooling improves outcome after globalischemia, focal ischemia, or traumatic brain injury. For this reason,hypothermia may be induced in order to reduce the effect of certainbodily injuries to the brain as well as other organs.

Cerebral hypothermia has traditionally been accomplished through wholebody cooling to create a condition of total body hypothermia in therange of 20° C. to 30° C. The currently-employed techniques and devicesused to cause total body hypothermia lead to various side effects. Inaddition to the undesirable side effects, present methods ofadministering total body hypothermia are cumbersome.

Catheters have been developed which are inserted into the bloodstream ofthe patient in order to induce total body hypothermia. For example, U.S.Pat. No. 3,425,419 to Dato describes a method and apparatus of loweringand raising the temperature of the human body. Dato induces moderatehypothermia in a patient using a rigid metallic catheter. The catheterhas an inner passageway through which a fluid, such as water, can becirculated. The catheter is inserted through the femoral vein and thenthrough the inferior vena cava as far as the right atrium and thesuperior vena cava. The Dato catheter has an elongated cylindrical shapeand is constructed from stainless steel. By way of example, Datosuggests the use of a catheter approximately 70 cm in length andapproximately 6 mm in diameter. Thus, the Dato device cools along thelength of a very elongated device. Use of the Dato device is highlycumbersome due to its size and lack of flexibility.

U.S. Pat. No. 5,837,003 to Ginsburg also discloses a method andapparatus for controlling a patient's body temperature. In thistechnique, a flexible catheter is inserted into the femoral artery orvein or the jugular vein. The catheter may be in the form of a balloonto allow an enhanced surface area for heat transfer. A thermallyconductive metal foil may be used as part of a heat-absorbing surface.This device fails to disclose or teach use of any ability to enhanceheat transfer. In addition, the disclosed device fails to disclosetemperature regulation.

An ailment particular susceptible to treatment by cooling, eitherselective or whole body, is fever or hyperthermia. There is a growingawareness of the dangers associated with fever. Many patients,especially after surgery and/or in the intensive care unit, suffer fromfever. For example, it is estimated that 90% of patients inneurointensive care units suffering from sub-arachnoid hemorrhage have afever. Further, 60% of patients in neurointensive care units sufferingfrom intra-cranial hemorrhage have a fever. 80% of patients inneurointensive care units suffering from traumatic brain injury have afever. These patients are typically treated with Tylenol, coolingblankets, or other such methods. These methods are not believed to bevery effective; moreover, they are difficult to control.

Therefore, a practical method and apparatus that lowers and controls thetemperature of the human body satisfies a long-felt need.

SUMMARY OF THE INVENTION

In one aspect, the apparatus of the present invention can include a heattransfer element that can be used to apply cooling to the blood flowingin a large vein feeding the heart.

The heat transfer element, by way of example only, includes first andsecond elongated, articulated segments, each segment having amixing-inducing exterior surface. A flexible joint can connect the firstand second elongated segments. An inner lumen may be disposed within thefirst and second elongated segments and is capable of transporting apressurized working fluid to a distal end of the first elongatedsegment. In addition, the first and second elongated segments may have amixing-inducing interior surface for inducing mixing within thepressurized working fluid. The mixing-inducing exterior surface may beadapted to induce mixing within a blood flow when placed within anartery or vein. In one embodiment, the flexible joint includes a bellowssection that also allows for axial compression of the heat transferelement as well as for enhanced flexibility. In alternative embodiments,the bellows section may be replaced with flexible tubing such as smallcylindrical polymer connecting tubes.

In one embodiment, the mixing-inducing exterior surfaces of the heattransfer element include one or more helical grooves and ridges.Adjacent segments of the heat transfer element can be oppositelyspiraled to increase mixing. For instance, the first elongated heattransfer segment may include one or more helical ridges having acounter-clockwise twist, while the second elongated heat transfersegment includes one or more helical ridges having a clockwise twist.Alternatively, of course, the first elongated heat transfer segment mayinclude one or more clockwise helical ridges, and the second elongatedheat transfer segment may include one or more counter-clockwise helicalridges. The first and second elongated, articulated segments may beformed from highly conductive materials such as metals, thin polymers,or doped polymers.

The heat transfer device may also have a supply catheter with an innercatheter lumen coupled to the inner lumen within the first and secondelongated heat transfer segments. A working fluid supply configured todispense the pressurized working fluid may be coupled to the innercatheter lumen or alternatively to the supply catheter. The workingfluid supply may be configured to produce the pressurized working fluidat a temperature of about 0° C. and at a pressure below about 5atmospheres of pressure.

In yet another alternative embodiment, the heat transfer device may havethree or more elongated, articulated, heat transfer segments each havinga mixing-inducing exterior surface, with additional flexible jointsconnecting the additional elongated heat transfer segments. In one suchembodiment, by way of example only, the first and third elongated heattransfer segments may include clockwise helical ridges, and the secondelongated heat transfer segment may include one or morecounter-clockwise helical ridges. Alternatively, of course, the firstand third elongated heat transfer segments may include counter-clockwisehelical ridges, and the second elongated heat transfer segment mayinclude one or more clockwise helical ridges.

The mixing-inducing exterior surface of the heat transfer element mayoptionally include a surface coating or treatment to inhibit clotformation. A surface coating may also be used to provide a degree oflubricity to the heat transfer element and its associated catheter.

The present invention is also directed to a method of treating fever inthe body by inserting a flexible cooling element into a vein that is inpressure communication with the heart, e.g., the femoral or iliac veins,the superior or inferior vena cavae or both. The vena cavae may beaccessed via known techniques from the jugular vein or from thesubclavian or femoral veins, for example. The heat transfer element inone or both vena cavae may then cool virtually all the blood beingreturned to the heart. The cooled blood enters the right atrium at whichpoint the same is pumped through the right ventricle and into thepulmonary artery to the lungs where the same is oxygenated. Due to theheat capacity of the lungs, the blood does not appreciably warm duringoxygenation. The cooled blood is returned to the heart and pumped to theentire body via the aorta. Thus, cooled blood may be deliveredindirectly to a chosen organ such as the brain. This indirect cooling isespecially effective as high blood flow organs such as the heart andbrain are preferentially supplied blood by the vasculature.

A warming blanket or other warming device may be applied to portions ofthe body to provide comfort to the patient and to inhibitthermoregulatory responses such as vasoconstriction. Thermoregulatorydrugs may also be so provided for this reason.

The method further includes circulating a working fluid through theflexible, conductive cooling element in order to lower the temperatureof the blood in the vena cava. The flexible, conductive heat transferelement preferably absorbs more than about 100 or 300 Watts of heat.

The method may also include inducing mixing within the free stream bloodflow within the vena cava. It is noted that a degree of turbulence ormixing is generally present within the vena cava anyway. The step ofcirculating may include inducing mixing in the flow of the working fluidthrough the flexible heat transfer element. The pressure of the workingfluid may be maintained below about 5 atmospheres of pressure.

The present invention also envisions a method for lowering a fever inthe body of a patient which includes introducing a catheter, with acooling element, into a vena cava supplying the heart, the catheterhaving a diameter of about 18 mm or less, inducing mixing in bloodflowing over the cooling element, and lowering the temperature of thecooling element to remove heat from the blood to cool the blood. In oneembodiment, the cooling step removes at least about 50 Watts of heatfrom the blood. The mixing induced may result in a Nusselt numberenhancement of the flow of between about 5 and 80.

Advantages of the invention are numerous. Patients can be provided withan efficient method of reducing fever that does not suffer from thedeleterious consequences of the prior art. The procedure can beadministered safely and easily. Numerous cardiac and neural settings canbenefit by the hypothermic therapy. Other advantages will be understoodfrom the following.

The novel features of this invention, as well as the invention itself,will be best understood from the attached drawings, taken along with thefollowing description, in which similar reference characters refer tosimilar parts, and in which:

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an elevation view of one embodiment of a heat transfer elementaccording to the invention;

FIG. 2 is a longitudinal section view of the heat transfer element ofFIG. 1;

FIG. 3 is a transverse section view of the heat transfer element of FIG.1;

FIG. 4 is a perspective view of the heat transfer element of FIG. 1 inuse within a blood vessel;

FIG. 5 is a schematic representation of the heat transfer element beingused in an embodiment within the superior vena cava; and

FIG. 6 is a flowchart showing an exemplary method of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Overview

A one or two-step process and a one or two-piece device may be employedto intravascularly lower the temperature of a body in order to treatfever. A cooling element may be placed in a high-flow vein such as thevena cavae to absorb heat from the blood flowing into the heart. Thistransfer of heat causes a cooling of the blood flowing through the heartand thus throughout the vasculature. Such a method and device maytherapeutically be used to treat fever.

A heat transfer element that systemically cools blood should be capableof providing the necessary heat transfer rate to produce the desiredcooling effect throughout the vasculature. This may be up to or greaterthan 300 watts, and is at least partially dependent on the mass of thepatient and the rate of blood flow. Surface features may be employed onthe heat transfer element to enhance the heat transfer rate. The surfacefeatures and other components of the heat transfer element are describedin more detail below.

One problem with treating fever with cooling is that the cause of thepatient's fever attempts to defeat the cooling. Thus, a high powerdevice is often required.

Anatomical Placement

The internal jugular vein is the vein that directly drains the brain.The external jugular joins the internal jugular at the base of the neck.The internal jugular veins join the subclavian veins to form thebrachiocephalic veins that in turn drain into the superior vena cava.The superior vena cava drains into the right atrium of the heart andsupplies blood to the heart from the upper part of the body.

A cooling element may be placed into the superior vena cava, inferiorvena cava, or otherwise into a vein which feeds into the superior venacava or otherwise into the heart to cool the body. A physician maypercutaneously place the catheter into the subclavian or internal orexternal jugular veins to access the superior vena cava. The blood,cooled by the heat transfer element, may be processed by the heart andprovided to the body in oxygenated form to be used as a conductivemedium to cool the body. The lungs have a fairly low heat capacity, andthus the lungs do not cause appreciable rewarming of the flowing blood.

The vasculature by its very nature provides preferential blood flow tothe high blood flow organs such as the brain and the heart. Thus, theseorgans are preferentially cooled by such a procedure. The core bodytemperature may be measured by an esophageal probe. The braintemperature usually decreases more rapidly than the core bodytemperature. The inventors believe this effect to be due to thepreferential supply of blood provided to the brain and heart. Thiseffect may be even more pronounced if thermoregulatory effects, such asvasoconstriction, occur that tend to focus blood supply to the corevascular system and away from the peripheral vascular system.

Heat Transfer

When a heat transfer element is inserted approximately coaxially into anartery or vein, the primary mechanism of heat transfer between thesurface of the heat transfer element and the blood is forced convection.Convection relies upon the movement of fluid to transfer heat. Forcedconvection results when an external force causes motion within thefluid. In the case of arterial or venous flow, the beating heart causesthe motion of the blood around the heat transfer element.

The magnitude of the heat transfer rate is proportional to the surfacearea of the heat transfer element, the temperature differential, and theheat transfer coefficient of the heat transfer element.

The receiving artery or vein into which the heat transfer element isplaced has a limited diameter and length. Thus, the surface area of theheat transfer element must be limited to avoid significant obstructionof the artery or vein and to allow the heat transfer element to easilypass through the vascular system. For placement within the superior venacava via the external jugular, the cross sectional diameter of the heattransfer element may be limited to about 5-6 mm, and its length may belimited to approximately 10-15 cm. For placement within the inferiorvena cava, the cross sectional diameter of the heat transfer element maybe limited to about 6-7 mm, and its length may be limited toapproximately 25-35 cm.

Decreasing the surface temperature of the heat transfer element canincrease the temperature differential. However, the minimum allowablesurface temperature is limited by the characteristics of blood. Bloodfreezes at approximately 0° C. When the blood approaches freezing, iceemboli may form in the blood, which may lodge downstream, causingserious ischemic injury. Furthermore, reducing the temperature of theblood also increases its viscosity, which results in a small decrease inthe value of the convection heat transfer coefficient. In addition,increased viscosity of the blood may result in an increase in thepressure drop within the artery, thus compromising the flow of blood tothe brain. Given the above constraints, it is advantageous to limit theminimum allowable surface temperature of the cooling element toapproximately 5° C. This results in a maximum temperature differentialbetween the blood stream and the cooling element of approximately 32° C.For other physiological reasons, there are limits on the maximumallowable surface temperature of the warming element.

However, in certain situations, temperatures lower than 0° C. may beused. For example, certain patients may have blood flows such that theflow per se prohibits or significantly inhibits freezing. To achievesuch cooling, sub-zero temperatures may be used. In these cases, workingfluids such as perfluorocarbons may be employed.

The mechanisms by which the value of the convection heat transfercoefficient may be increased are complex. However, it is well known thatthe convection heat transfer coefficient increases with the level of“mixing” or “turbulent” kinetic energy in the fluid flow. Thus it isadvantageous to have blood flow with a high degree of mixing in contactwith the heat transfer element.

The blood flow has a considerably more stable flux in the vena cava thanin an artery. However, the blood flow in the vena cava still has a highdegree of inherent mixing or turbulence. Reynolds numbers in thesuperior vena cava may range, for example, from 2,000 to 5,000. Thus,blood cooling in the vena cava may benefit from enhancing the level ofmixing with the heat transfer element but this benefit may besubstantially less than that caused by the inherent mixing.

Boundary Layers

A thin boundary layer has been shown to form during the cardiac cycle.Boundary layers develop adjacent to the heat transfer element as well asnext to the walls of the artery or vein. Each of these boundary layershas approximately the same thickness as the boundary layer that wouldhave developed at the wall of the artery in the absence of the heattransfer element. The free stream flow region is developed in an annularring around the heat transfer element. The heat transfer element used insuch a vessel should reduce the formation of such viscous boundarylayers.

Heat Transfer Element Characteristics and Description

The intravascular heat transfer element should be flexible in order tobe placed within the vena cavae or other veins or arteries. Theflexibility of the heat transfer element is an important characteristicbecause the same is typically inserted into a vein such as the externaljugular and accesses the vena cava by initially passing though a seriesof one or more branches. Further, the heat transfer element is ideallyconstructed from a highly thermally conductive material such as metal inorder to facilitate heat transfer. The use of a highly thermallyconductive material increases the heat transfer rate for a giventemperature differential between the working fluid within the heattransfer element and the blood. This facilitates the use of a highertemperature coolant, or lower temperature warming fluid, within the heattransfer element, allowing safer working fluids, such as water orsaline, to be used. Highly thermally conductive materials, such asmetals, tend to be rigid. Therefore, the design of the heat transferelement should facilitate flexibility in an inherently inflexiblematerial.

However, balloon designs may also be employed, such as those disclosedin co-pending U.S. patent application Ser. No. 09/215,038, filed Dec.16, 1998, entitled “Inflatable Catheter for Selective Organ Heating andCooling and Method of Using the Same,”, now U.S. Pat. No. 6,261,312 andincorporated herein by reference in its entirety.

It is estimated that the cooling element should absorb at least about 50Watts of heat when placed in the vena cava to lower the temperature ofthe body to between about 30° C. and 34° C. These temperatures arethought to be appropriate to lower most fevers. The power removeddetermines how quickly the target temperature can be reached. Forexample, in a fever therapy in which it is desired to lower braintemperature, the same may be lowered about 4° C. per hour in a 70 kghuman upon removal of 300 Watts.

One embodiment of the invention uses a modular design. This designcreates helical blood flow and produces a level of mixing in the bloodflow by periodically forcing abrupt changes in the direction of thehelical blood flow. The abrupt changes in flow direction are achievedthrough the use of a series of two or more heat transfer segments, eachincluded of one or more helical ridges. The use of periodic abruptchanges in the helical direction of the blood flow in order to inducestrong free stream turbulence may be illustrated with reference to acommon clothes washing machine. The rotor of a washing machine spinsinitially in one direction causing laminar flow. When the rotor abruptlyreverses direction, significant turbulent kinetic energy is createdwithin the entire wash basin as the changing currents cause randomturbulent motion within the clothes-water slurry. These surface featuresalso tend to increase the surface area of the heat transfer element,further enhancing heat transfer.

FIG. 1 is an elevation view of one embodiment of a cooling element 14according to the present invention. The heat transfer element 14includes a series of elongated, articulated segments or modules 20, 22,24. Three such segments are shown in this embodiment, but two or moresuch segments could be used without departing from the spirit of theinvention. As seen in FIG. 1, a first elongated heat transfer segment 20is located at the proximal end of the heat transfer element 14. Amixing-inducing exterior surface of the segment 20 includes fourparallel helical ridges 28 with four parallel helical grooves 26therebetween. One, two, three, or more parallel helical ridges 28 couldalso be used without departing from the spirit of the present invention.In this embodiment, the helical ridges 28 and the helical grooves 26 ofthe heat transfer segment 20 have a left hand twist, referred to hereinas a counter-clockwise spiral or helical rotation, as they proceedtoward the distal end of the heat transfer segment 20.

The first heat transfer segment 20 is coupled to a second elongated heattransfer segment 22 by a first bellows section 25, which providesflexibility and compressibility. The second heat transfer segment 22includes one or more helical ridges 32 with one or more helical grooves30 therebetween. The ridges 32 and grooves 30 have a right hand, orclockwise, twist as they proceed toward the distal end of the heattransfer segment 22. The second heat transfer segment 22 is coupled to athird elongated heat transfer segment 24 by a second bellows section 27.The third heat transfer segment 24 includes one or more helical ridges36 with one or more helical grooves 34 therebetween. The helical ridge36 and the helical groove 34 have a left hand, or counter-clockwise,twist as they proceed toward the distal end of the heat transfer segment24. Thus, successive heat transfer segments 20, 22, 24 of the heattransfer element 14 alternate between having clockwise andcounterclockwise helical twists. The actual left or right hand twist ofany particular segment is immaterial, as long as adjacent segments haveopposite helical twist.

In addition, the rounded contours of the ridges 28, 32, 36 allow theheat transfer element 14 to maintain a relatively atraumatic profile,thereby minimizing the possibility of damage to the blood vessel wall. Aheat transfer element according to the present invention may includetwo, three, or more heat transfer segments.

The bellows sections 25, 27 are formed from seamless and nonporousmaterials, such as metal, and therefore are impermeable to gas, whichcan be particularly important, depending on the type of working fluidthat is cycled through the heat transfer element 14. The structure ofthe bellows sections 25, 27 allows them to bend, extend and compress,which increases the flexibility of the heat transfer element 14 so thatit is more readily able to navigate through blood vessels. The bellowssections 25, 27 also provide for axial compression of the heat transferelement 14, which can limit the trauma when the distal end of the heattransfer element 14 abuts a blood vessel wall. The bellows sections 25,27 are also able to tolerate cryogenic temperatures without a loss ofperformance. In alternative embodiments, the bellows may be replaced byflexible polymer tubes, which are bonded between adjacent heat transfersegments.

The exterior surfaces of the heat transfer element 14 can be made frommetal, and may include very high thermal conductivity materials such asnickel, thereby facilitating heat transfer. Alternatively, other metalssuch as stainless steel, titanium, aluminum, silver, copper and thelike, can be used, with or without an appropriate coating or treatmentto enhance biocompatibility or inhibit clot formation. Suitablebiocompatible coatings include, e.g., gold, platinum or polymerparalyene. The heat transfer element 14 may be manufactured by plating athin layer of metal on a mandrel that has the appropriate pattern. Inthis way, the heat transfer element 14 may be manufactured inexpensivelyin large quantities, which is an important feature in a disposablemedical device.

Because the heat transfer element 14 may dwell within the blood vesselfor extended periods of time, such as 24-48 hours or even longer, it maybe desirable to treat the surfaces of the heat transfer element 14 toavoid clot formation. In particular, one may wish to treat the bellowssections 25, 27 because stagnation of the blood flow may occur in theconvolutions, thus allowing clots to form and cling to the surface toform a thrombus. One means by which to prevent thrombus formation is tobind an antithrombogenic agent to the surface of the heat transferelement 14. For example, heparin is known to inhibit clot formation andis also known to be useful as a biocoating. Alternatively, the surfacesof the heat transfer element 14 may be bombarded with ions such asnitrogen. Bombardment with nitrogen can harden and smooth the surfaceand thus prevent adherence of clotting factors. Another coating thatprovides beneficial properties may be a lubricious coating. Lubriciouscoatings, on both the heat transfer element and its associated catheter,allow for easier placement in the, e.g., vena cava.

FIG. 2 is a longitudinal sectional view of the heat transfer element 14of an embodiment of the invention, taken along line 2-2 in FIG. 1. Someinterior contours are omitted for purposes of clarity. An inner tube 42creates an inner lumen 40 and an outer lumen 46 within the heat transferelement 14. Once the heat transfer element 14 is in place in the bloodvessel, a working fluid such as saline or other aqueous solution may becirculated through the heat transfer element 14. Fluid flows up a supplycatheter into the inner lumen 40. At the distal end of the heat transferelement 14, the working fluid exits the inner lumen 40 and enters theouter lumen 46. As the working fluid flows through the outer lumen 46,heat is transferred from the working fluid to the exterior surface 37 ofthe heat transfer element 14. Because the heat transfer element 14 isconstructed from a high conductivity material, the temperature of itsexterior surface 37 may reach very close to the temperature of theworking fluid. The tube 42 may be formed as an insulating divider tothermally separate the inner lumen 40 from the outer lumen 46. Forexample, insulation may be achieved by creating longitudinal airchannels in the wall of the insulating tube 42. Alternatively, theinsulating tube 42 may be constructed of a non-thermally conductivematerial like polytetrafluoroethylene or another polymer.

It is important to note that the same mechanisms that govern the heattransfer rate between the exterior surface 37 of the heat transferelement 14 and the blood also govern the heat transfer rate between theworking fluid and the interior surface 38 of the heat transfer element14. The heat transfer characteristics of the interior surface 38 areparticularly important when using water, saline or other fluid thatremains a liquid as the working fluid. Other coolants such as Freonundergo nucleate boiling and create mixing through a differentmechanism. Saline is a safe working fluid, because it is non-toxic, andleakage of saline does not result in a gas embolism, which could occurwith the use of boiling refrigerants. Since mixing in the working fluidis enhanced by the shape of the interior surface 38 of the heat transferelement 14, the working fluid can be delivered to the cooling element 14at a warmer temperature and still achieve the necessary cooling rate.Similarly, since mixing in the working fluid is enhanced by the shape ofthe interior surface of the heat transfer element, the working fluid canbe delivered to the warming element 14 at a cooler temperature and stillachieve the necessary warming rate.

This has a number of beneficial implications in the need for insulationalong the catheter shaft length. Due to the decreased need forinsulation, the catheter shaft diameter can be made smaller. Theenhanced heat transfer characteristics of the interior surface of theheat transfer element 14 also allow the working fluid to be delivered tothe heat transfer element 14 at lower flow rates and lower pressures.High pressures may make the heat transfer element stiff and cause it topush against the wall of the blood vessel, thereby shielding part of theexterior surface 37 of the heat transfer element 14 from the blood.Because of the increased heat transfer characteristics achieved by thealternating helical ridges 28, 32, 36, the pressure of the working fluidmay be as low as 5 atmospheres, 3 atmospheres, 2 atmospheres or evenless than 1 atmosphere.

FIG. 3 is a transverse sectional view of the heat transfer element 14 ofthe invention, taken at a location denoted by the line 3-3 in FIG. 1.FIG. 3 illustrates a five-lobed embodiment, whereas FIG. 1 illustrates afour-lobed embodiment. As mentioned earlier, any number of lobes mightbe used. In FIG. 3, the construction of the heat transfer element 14 isclearly shown. The inner lumen 40 is defined by the insulating tube 42.The outer lumen 46 is defined by the exterior surface of the insulatingtube 42 and the interior surface 38 of the heat transfer element 14. Inaddition, the helical ridges 32 and helical grooves 30 may be seen inFIG. 3. Although FIG. 3 shows four ridges and four grooves, the numberof ridges and grooves may vary. Thus, heat transfer elements with 1, 2,3, 4, 5, 6, 7, 8 or more ridges are specifically contemplated.

FIG. 4 is a perspective view of a heat transfer element 14 in use withina blood vessel, showing only one helical lobe per segment for purposesof clarity. Beginning from the proximal end of the heat transfer element(not shown in FIG. 4), as the blood moves forward, the first helicalheat transfer segment 20 induces a counter-clockwise rotational inertiato the blood. As the blood reaches the second segment 22, the rotationaldirection of the inertia is reversed, causing mixing within the blood.Further, as the blood reaches the third segment 24, the rotationaldirection of the inertia is again reversed. The sudden changes in flowdirection actively reorient and randomize the velocity vectors, thusensuring mixing throughout the bloodstream. During such mixing, thevelocity vectors of the blood become more random and, in some cases,become perpendicular to the axis of the vessel. Thus, a large portion ofthe volume of warm blood in the vessel is actively brought in contactwith the heat transfer element 14, where it can be cooled by directcontact rather than being cooled largely by conduction through adjacentlaminar layers of blood.

Referring back to FIG. 1, the heat transfer element 14 has been designedto address all of the design criteria discussed above. First, the heattransfer element 14 is flexible and is made of a highly conductivematerial. The flexibility is provided by a segmental distribution ofbellows sections 25, 27 that provide an articulating mechanism. Bellowshave a known convoluted design that provide flexibility. Second, theexterior surface area 37 has been increased through the use of helicalridges 28, 32, 36 and helical grooves 26, 30, 34. The ridges also allowthe heat transfer element 14 to maintain a relatively atraumaticprofile, thereby minimizing the possibility of damage to the vesselwall. Third, the heat transfer element 14 has been designed to promotemixing both internally and externally. The modular or segmental designallows the direction of the grooves to be reversed between segments. Thealternating helical rotations create an alternating flow that results inmixing the blood in a manner analogous to the mixing action created bythe rotor of a washing machine that switches directions back and forth.This action is intended to promote mixing to enhance the heat transferrate. The alternating helical design also causes beneficial mixing, orturbulent kinetic energy, of the working fluid flowing internally.

Method of Use

The practice of the present invention is illustrated in the followingnon-limiting example.

Exemplary Procedure

-   -   1. The patient is initially assessed as having a fever,        resuscitated, and stabilized.    -   2. The procedure may be carried out in an angiography suite,        NICU, ICU, or surgical suite equipped with fluoroscopy.    -   3. An ultrasound or angiogram of the superior vena cava and        external jugular can be used to determine the vessel diameter        and the blood flow; a catheter with an appropriately sized heat        transfer element can be selected.    -   4. After assessment of the veins, the patient is sterilely        prepped and infiltrated with lidocaine at a region where the        appropriate vein may be accessed.    -   5. The external jugular is cannulated and a guide wire may be        inserted to the superior vena cava. Placement of the guide wire        is confirmed with fluoroscopy.    -   6. An angiographic catheter can be fed over the wire and        contrast media injected into the vein to further to assess the        anatomy if desired.    -   7. Alternatively, the external jugular is cannulated and a        10-12.5 french (f) introducer sheath is placed.    -   8. A guide catheter is placed into the superior vena cava. If a        guide catheter is placed, it can be used to deliver contrast        media directly to further assess anatomy.    -   9. The cooling catheter is placed into the superior vena cava        via the guiding catheter or over the guidewire.    -   10. Placement is confirmed if desired with fluoroscopy.    -   11. Alternatively, the cooling catheter shaft has sufficient        pushability and torqueability to be placed in the superior vena        cava without the aid of a guide wire or guide catheter.    -   12. The cooling catheter is connected to a pump circuit also        filled with saline and free from air bubbles. The pump circuit        has a heat exchange section that is immersed into a water bath        and tubing that is connected to a peristaltic pump. The water        bath is chilled to approximately 0° C.    -   13. Cooling is initiated by starting the pump mechanism. The        saline within the cooling catheter is circulated at 5 cc/sec.        The saline travels through the heat exchanger in the chilled        water bath and is cooled to approximately 1° C.    -   14. The saline subsequently enters the cooling catheter where it        is delivered to the heat transfer element. The saline is warmed        to approximately 5-7° C. as it travels along the inner lumen of        the catheter shaft to the end of the heat transfer element.    -   15. The saline then flows back through the heat transfer element        in contact with the inner metallic surface. The saline is        further warmed in the heat transfer element to 12-15° C., and in        the process, heat is absorbed from the blood, cooling the blood        to 30° C. to 35° C.    -   16. The chilled blood then goes on to chill the body. It is        estimated that less than an hour will be required to        substantially reduce a fever down to normothermia.    -   17. The warmed saline travels back the outer lumen of the        catheter shaft and is returned to the chilled water bath where        the same is cooled to 1° C.    -   18. The pressure drops along the length of the circuit are        estimated to be between 1 and 10 atmospheres.    -   19. The cooling can be adjusted by increasing or decreasing the        flow rate of the saline. Monitoring of the temperature drop of        the saline along the heat transfer element will allow the flow        to be adjusted to maintain the desired cooling effect.    -   20. The catheter is left in place to provide cooling for, e.g.,        6-48 hours.

Of course, the use of the superior vena cava is only exemplary. It isenvisioned that the following veins may be appropriate to percutaneouslyinsert the heat transfer element: femoral, internal jugular, subclavian,and other veins of similar size and position. It is also envisioned thatthe following veins may be appropriate in which to dispose the heattransfer element during use: inferior vena cava, superior vena cava,femoral, internal jugular, and other veins of similar size and position.Arteries may also be employed if a fever therapy selective to aparticular organ or region of the body is desired.

FIG. 5 shows a cross-section of the heart in which the heat transferelement 14 is disposed in the superior vena cava 62. The heat transferelement 14 has rotating helical grooves 22 as well as counter-rotatinghelical grooves 24. Between the rotating and the counter-rotatinggrooves are bellows 27. It is believed that a design of this naturewould enhance the Nusselt number for the flow in the superior vena cavaby about 5 to 80.

In some cases, a heating blanket may be used. The heating blanket servesseveral purposes. By warming the patient, vasoconstriction is avoided.The patient is also made more comfortable. For example, it is commonlyagreed that for every one degree of core body temperature reduction, thepatient will continue to feel comfortable if the same experiences a risein surface area (skin) temperature of five degrees. Spasms due to totalbody hypothermia may be avoided. Temperature control of the patient maybe more conveniently performed as the physician has another variable(the amount of heating) which may be adjusted.

As an alternative, the warming element may be any of the heating methodsproposed in U.S. patent application Ser. No. 09/292,532, filed on Apr.15, 1999, and entitled “Isolated Selective Organ Cooling Method andApparatus,” and incorporated by reference above.

Anti-shivering drugs may be used to provide the features of the heatingblanket. In this connection, meperidine is an analgesic of the phenylpiperdine class that is known to bind to the opiate receptor. Meperidinemay be used to treat shivering due to post-operative anesthesia as wellas hypothermia induced in a fever suppression treatment.

In a method according to an embodiment of the invention for treatingpatients with fever, the heat transfer element as described may beplaced in any of several veins, including the femoral, the IVC, the SVC,the subclavian, the braichiocephalic, the jugular, and other such veins.The heat transfer element may also be placed in appropriate arteries formore selective fever reduction.

The amount of cooling performed may be judged to a first approximationby the rate of cool-down. The amount of cooling is proportional to thedifference between the temperature of the blood and the temperature ofthe heat transfer element or cooling element. Thus, if the temperatureof the blood is 40° C. and the temperature of the cooling element is 5°C., the power extracted will be greater than if the temperature of theblood is 38° C. and the temperature of the cooling element is maintainedat 5° C. Thus, the cool-down or cooling rate is generally greatest atthe beginning of a cooling procedure. Once the patient temperaturebegins to approach the target temperature, usually normothermia or 37oC,the cooling rate may be reduced because the temperature differential isno longer as great.

In any case, once the patient reaches the normothermic temperature, itis no longer easy to guess whether, in the absence of the coolingtherapy, the patient would otherwise be feverish or whether the feverhas abated. One embodiment of the invention allows a determination ofthis.

First, it is noted that the power extracted can be calculated from thetemperature differential between the working fluid supply temperatureand the working fluid return temperature. In particular:P _(catheter) =M c _(f) ΔT _(f)Where P_(catheter) is the power extracted, M is the mass flow rate ofthe working fluid, c_(f) is the heat capacity of the working fluid, andΔT is the temperature differential between the working fluid as itenters the catheter and as it exits the catheter. Accordingly,P_(catheter) can be readily calculated by measuring the mass flow of thecirculating fluid and the temperature difference between the workingfluid as it enters and exits the catheter. The power removed by thecatheter as determined above may be equated to a close approximation tothe power that is lost by the patient's body.

In general, a closed-form solution for the power P required to cool (orheat) a body at temperature T to temperature T₀ is not known. Onepossible approximation may be to assume an exponential relationship:P=α(exp β(T−T ₀)−1)

Taking the derivative of each side with respect to temperature:$\frac{\partial P}{\partial T} = {\alpha\quad{\beta\mathbb{e}}^{\beta{({T - T_{0}})}}}$and taking the inverse of each side:$\frac{\partial T}{\partial P} = \frac{1}{\alpha\quad{\beta\mathbb{e}}^{\beta{({T - T_{0}})}}}$or${\Delta\quad T} \approx {\frac{\partial T}{\partial P}\Delta\quad P}$where ΔT is the temperature differential from nominal temperature and ΔPis the measured power.

A close approximation may be obtained by assuming the relationship islinear. Equivalently, a power series expansion may be taken, and thelinear term retained.

In any case, integrating, assuming a linear relationship, andrearranging:

P=α(T−T₀), where the constant of proportionality has units ofwatts/degree Celsius. One can determine the constant of proportionalityα using two points during the therapy when both T and P are finite andknown. One may be when therapy begins, i.e., when the patient hastemperature T and the catheter is drawing power P. Another point may beobtained when T=T₀ and P=P₀.

Then, for any P, T is given by:$T_{{absence}\quad{of}\quad{therapy}} = {T_{0} + \frac{P_{{at}\quad T_{0}}}{\alpha}}$

An example of this may be seen in FIG. 6, which shows a flowchart of anembodiment of a method of the invention. Referring to the figure, apatient presents at a hospital or clinic with a fever (step 202).Generally, such a patient will have a fever as a result of a malady orother illness for which hospitalization is required. For example, themajority of patients in ICUs present with a fever.

A catheter with a heat transfer element thereon may be inserted (step204). The initial power withdrawn P_(start) and body temperatureT_(start) may be measured (step 206), and the therapy begun (step 208).The therapy continues (step 210), and P and T are periodically,continuously, or otherwise measured (step 212). The measured T iscompared to the normothermic T=T₀, which is usually about 37° C. (step214). If T is greater than T0, the therapy continues (step 210). If T isless than T₀, then the power P₀ is measured at T=T₀ (step 216). By theequations above, a constant of proportionality α may be uniquelydetermined (step 218) by knowledge of T_(start), P_(start), P₀, and T₀.From α, T_(start), P_(start), P₀, and T₀, T_(absence of cooling) may bedetermined (step 220). T_(absence of cooling) is then compared to T₀(step 222). If T_(absence of cooling)>T₀, then the patient is stillgenerating enough power via their metabolism to cause a fever if thetherapy were discontinued. Thus, therapy is continued (step 224). IfT_(absence of cooling)<=T₀, then the patient is no longer generatingenough power via their metabolism to cause a fever if the therapy werediscontinued. Thus, therapy is discontinued (step 226). Variations ofthe above method will be apparent to those of ordinary skill in the art.

While the invention herein disclosed is capable of obtaining the objectshereinbefore stated, it is to be understood that this disclosure ismerely illustrative of the presently preferred embodiments of theinvention and that no limitations are intended other than as describedin the appended claims.

1. A method for treating fever in a patient's body intravascularly,comprising: providing a catheter having a cooling element attached to adistal end thereof, wherein said cooling element comprises a pluralityof heat transfer segments each having a plurality of exterior surfaceirregularities being shaped and arranged to create repetitively changingdirections of flow in surrounding fluid; inserting the catheter throughthe vascular system of a patient with a fever to place the coolingelement in a vein that drains into the heart of a patient; circulatingfluid through the cooling element; transferring heat from the blood inthe vein to the cooling element; and thereby lowering the temperature ofthe patient.
 2. The method of claim 1, wherein the surfaceirregularities each include a helical ridge and a helical groove formedon each heat transfer segment, the helical ridge on each heat transfersegment having an opposite helical twist to the helical ridges onadjacent heat transfer segments.
 3. The method of claim 1, wherein eachof the plurality of heat transfer segments are connected to adjacentheat transfer segments by a flexible joint.
 4. The method of claim 1,further wherein the flexible joint includes a bellows.
 5. The method ofclaim 1, further comprising inducing mixing in the blood of the vascularsystem of the patient.
 6. The method of claim 1, further comprisingadministering a thermoregulatory drug to the patient.
 7. The method ofclaim 6, wherein the thermoregulatory drug is selected from the groupconsisting of clonidine, meperidine, propofol, magnesium,dexmedetomidine, and combinations thereof.
 8. The method of claim 1,wherein the cooling element is disposed in a vein selected from thegroup consisting of the superior vena cava, the inferior vena cava, thefemoral, the iliac, the subclavian, the braichiocephalic, orcombinations of these.
 9. A method for determining duration of aintravascular fever treatment, comprising: providing a catheter having acooling element attached to a distal end thereof, wherein said coolingelement comprises a plurality of heat transfer segments each having aplurality of exterior surface irregularities being shaped and arrangedto create repetitively changing directions of flow in surrounding fluid;inserting the catheter through the vascular system of a patient with afever to place the cooling element in a vein that drains into the heartof a patient; circulating fluid through the cooling element, andmeasuring a starting power withdrawn and starting body temperature atthe beginning of the circulating; transferring heat from the blood inthe vein to the cooling element, and thereby lowering the temperature ofthe patient; measuring a power withdrawn and body temperature during thecirculating; measuring a power withdrawn at substantially the time whenthe body temperature equals a normothermic temperature; calculating aT_(absence of cooling) from the power withdrawn at substantially thetime when the body temperature equals a normothermic temperature, thenormothermic temperature, the starting power withdrawn and the startingbody temperature; and comparing the T_(absence of cooling) with thenormothermic temperature, and continuing the circulating ifT_(absence of cooling) is greater than the normothermic temperature, anddiscontinuing the circulating if T_(absence of cooling) is less than thenormothermic temperature.
 10. The method of claim 9, wherein the surfaceirregularities each include a helical ridge and a helical groove formedon each heat transfer segment, the helical ridge on each heat transfersegment having an opposite helical twist to the helical ridges onadjacent heat transfer segments.
 11. The method of claim 9, wherein eachof the plurality of heat transfer segments are connected to adjacentheat transfer segments by a flexible joint.
 12. The method of claim 9,further wherein the flexible joint includes a bellows.
 13. A computerprogram, residing on a computer-readable medium, containing instructionsfor causing a chiller console, circulating set, and intravascularlyinserted catheter having a heat transfer element at a distal end thereofto: circulate fluid through a heat transfer element, wherein said heattransfer element includes a plurality of heat transfer segments eachhaving a plurality of exterior surface irregularities being shaped andarranged to create repetitively changing directions of flow insurrounding fluid, and measuring a starting power withdrawn and startingbody temperature corresponding to a body temperature of a patient at thebeginning of the circulating; transfer heat from the blood in thevasculature to the heat transfer element, and thereby lowering the bodytemperature of a patient; measure a power withdrawn and body temperatureduring the circulating; measure a power withdrawn at substantially thetime when the body temperature equals a normothermic temperature;calculate a T_(absence of cooling) from: the power withdrawn atsubstantially the time when the body temperature equals a normothermictemperature, the normothermic temperature, the starting power withdrawn,and the starting body temperature; and compare theT_(absence of cooling) with the normothermic temperature, and continuingthe circulating if T_(absence of cooling) is greater than thenormothermic temperature, and discontinuing the circulating ifT_(absence of cooling) is less than the normothermic temperature. 14.The method of claim 13, wherein the surface irregularities each includea helical ridge and a helical groove formed on each heat transfersegment, the helical ridge on each heat transfer segment having anopposite helical twist to the helical ridges on adjacent heat transfersegments.
 15. The method of claim 13, wherein each of the plurality ofheat transfer segments are connected to adjacent heat transfer segmentsby a flexible joint.
 16. The method of claim 13, further wherein theflexible joint includes a bellows.